Dataset Information

Matrisome of neonatal mouse dermal fibroblasts

ABSTRACT: The goal of this project is to compare the protein composition of the extracellular matrices (ECMs) deposited in vitro by wild type, heterozygous, or SPAG17 KO neonatal mouse dermal fibroblasts.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Fibroblast, Skin Fibroblast

SUBMITTER: George Chlipala

LAB HEAD: Alexandra Naba

PROVIDER: PXD019869 | Pride | 2022-09-22

REPOSITORIES: Pride

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Publications

Reduced SPAG17 Expression in Systemic Sclerosis Triggers Myofibroblast Transition and Drives Fibrosis.

Sapao Paulene P Roberson Elisha D O EDO Shi Bo B Assassi Shervin S Skaug Brian B Lee Fred F Naba Alexandra A Perez White Bethany E BE Córdova-Fletes Carlos C Tsou Pei-Suen PS Sawalha Amr H AH Gudjonsson Johann E JE Ma Feiyang F Verma Priyanka P Bhattacharyya Dibyendu D Carns Mary M Strauss Jerome F JF Sicard Delphine D Tschumperlin Daniel J DJ Champer Melissa I MI Campagnola Paul J PJ Teves Maria E ME Varga John J

The Journal of investigative dermatology 20220915 2

Systemic sclerosis (SSc) is a clinically heterogeneous fibrotic disease with no effective treatment. Myofibroblasts are responsible for unresolving synchronous skin and internal organ fibrosis in SSc, but the drivers of sustained myofibroblast activation remain poorly understood. Using unbiased transcriptome analysis of skin biopsies, we identified the downregulation of SPAG17 in multiple independent cohorts of patients with SSc, and by orthogonal approaches, we observed a significant negative c ...[more]

PMID: 36116512

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Project description:Lymphedema (LD) is characterized by the accumulation of protein-rich interstitial fluid, lipids and a significant inflammatory cell infiltrate in the limb. It causes a significant morbidity and is a common disabling disease affecting more than 150 million people worldwide, however there is no yet curative treatment. In this study, we found that LD tissues from patients exhibit inflamed gene expression profile compared to their normal arm. This was next confirmed by a lipidomic analysis that revealed severe decrease in arachidonic acid-derived lipid mediators generated by the 15-lipoxygenase (15-LO) in lymphedematous arms. Using a mouse model of lymphedema, we reproduced the etiology of the human pathology including the loss of specialized pro-resolving lipid mediators that play essential role in resolution of inflammation. This was associated with a lack of nonlymphoid PPAR-positive regulatory T cells (Treg) recruitment in the injured limb adipose tissue. Importantly, we identified the lymphatic endothelial 15-LO as responsible for the chemoattraction and survival of this Treg subpopulation. These results were confirmed by an aggravation of LD and degradation of the lymphatic network in an original transgenic mouse model in which ALOX15 gene has been selectively deleted in the lymphatic system (ALOX15lecKO). Importantly, this phenotype was rescued by the injection of ALOX15-expressing lentivectors. These results provide evidence that lymphatic 15-LO may represent a novel therapeutic target for LD by serving as a mediator of nonlymphoid Treg cell population invasion into lymphedematous adipose tissue to resolve inflammation. Experimental workflow: To broadly identify gene expression signatures associated to secondary LD, we performed bulk-RNA sequencing on dermolipectomy tissue samples from women who developed LD after breast cancer. Four patient biopsies (normal arm and LD arm in each patient) were studied and the differential expression analysis (DEseq) followed by a protein-coding RNA profiling.

Dataset Information

Matrisome of neonatal mouse dermal fibroblasts

Publications

Reduced SPAG17 Expression in Systemic Sclerosis Triggers Myofibroblast Transition and Drives Fibrosis.

Similar Datasets

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